Mitochondrial dysfunction in reproductive and developmental toxicity

Palmeira, Carlos M.; Machado, Ivo F.; Ramalho‐Santos, João

doi:10.1016/b978-0-323-89773-0.00054-0

Cited by 2 publications

(3 citation statements)

References 168 publications

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“…40 To quantify the mitochondrial membrane potential change after PFHxS and PFOS exposure, TMRM, a small cationic lipophilic fluorescent indicator 41 , was used to bind negatively charged mitochondrial membrane. 42 Our results show that the red signal of TMRM was dimmer in PFHxS and PFOS treatment groups, again, depending on the carbon-chain lengths (Fig. 3C).…”

Section: Resultsmentioning

confidence: 51%

Adverse PFAS effects on mouse oocyte in vitro maturation are associated with carbon-chain length and inclusion of a sulfonate group

Feng

Soto‐Moreno

Prakash

et al. 2022

Preprint

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Per- and polyfluoroalkyl substances (PFAS) are man-made chemicals that are used in products such as non-stick cookware, stain-resistant coating, and food packaging. PFAS are characterized by their fluorinated carbon chains that make them hard to degrade and bioaccumulate in human and animals. Toxicological studies have shown PFAS toxic effects: cytotoxicity, immunotoxicity, neurotoxicity, and reproductive toxicity. Two major categories of PFAS are perfluoroalkyl carboxylic acid (PFCA) and perfluoroalkyl sulfonic acid (PFSA). In this study, we used a mouse-oocyte-in-vitro-maturation (IVM) system to study how the structures of PFAS, such as carbon-chain length and functional groups, determine their reproductive toxicity. We found the toxicity of PFAS is elevated with increasing carbon-chain length and the inclusion of the sulfonate group. Specifically, at 600 μM, perfluorohexanesulfonic acid (PFHxS) and perfluorooctanesulfonic acid (PFOS) reduced the rates of both germinal vesicle breakdown (GVBD) and polar body extrusion (PBE) as well as induced the formation of relatively large polar bodies. However, the shorter PFSA, perfluorobutanesulfonic acid (PFBS), and all PFCA did not show similar adverse cytotoxicity. We further examined mitochondria and cytoskeleton, two essential factors for cell division, in PFOS- and PFHxS-treated oocytes. We found that 600 μM PFHxS and PFOS exposure induced excess reactive oxygen species (ROS) and decreased mitochondrial membrane potential (MMP). Cytoskeleton analysis revealed that PFHxS and PFOS exposure induced chromosome misalignment, abnormal F-actin organization, elongated the spindle formation, and symmetric division in the treated oocytes. Together, our study provides new information on the structure-toxicity relationship of PFAS.

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Section: Resultsmentioning

confidence: 51%

Adverse PFAS effects on mouse oocyte in vitro maturation are associated with carbon-chain length and inclusion of a sulfonate group

Feng

Soto‐Moreno

Prakash

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…39 To quantify the mitochondrial membrane potential change after PFHxS and PFOS exposure, TMRM, a small cationic lipophilic fluorescent indicator, 40 was used to bind negatively charged mitochondrial membrane. 41 Our results show that the red signal of TMRM was dimmer in PFHxS and PFOS treatment groups, again, depending on the carbon-chain lengths (Figure 3C). Statistically, the red signal intensity is 3.14 ± 0.09 in control, while it is 2.81 ± 0.10 in the PFHxS-treatment group (p < 0.05 vs. control) and 2.12 ± 0.06 in the PFOS-treatment group (p < 0.001 vs. control and PFHxS group).…”

Section: Pfhxs and Pfos Induce Mitochondrial Depolarizationmentioning

confidence: 56%

“…A positive loop exists between mitochondrion‐derived ROS accumulation and mitochondrial depolarization, 38 an event that is universally associated with apoptosis and cell death 39 . To quantify the mitochondrial membrane potential change after PFHxS and PFOS exposure, TMRM, a small cationic lipophilic fluorescent indicator, 40 was used to bind negatively charged mitochondrial membrane 41 . Our results show that the red signal of TMRM was dimmer in PFHxS and PFOS treatment groups, again, depending on the carbon‐chain lengths (Figure 3C).…”

Section: Resultsmentioning

confidence: 99%

Adverse PFAS effects on mouse oocyte in vitro maturation are associated with carbon‐chain length and inclusion of a sulfonate group

et al. 2022

View full text Add to dashboard Cite

Objectives: Per-and polyfluoroalkyl substances (PFAS) are man-made chemicals that are widely used in various products. PFAS are characterized by their fluorinated carbon chains that make them hard to degrade and bioaccumulate in human and animals. Toxicological studies have shown PFAS toxic effects: cytotoxicity, immunotoxicity, neurotoxicity, and reproductive toxicity. However, it is still unclear how the structures of PFAS, such as carbon-chain length and functional groups, determine their reproductive toxicity.Methods and Results: By using a mouse-oocyte-in-vitro-maturation (IVM) system, we found the toxicity of two major categories of PFAS, perfluoroalkyl carboxylic acid (PFCA) and perfluoroalkyl sulfonic acid (PFSA), is elevated with increasing carbonchain length and the inclusion of the sulfonate group. Specifically, at 600 μM, perfluorohexanesulfonic acid (PFHxS) and perfluorooctanesulfonic acid (PFOS) reduced the rates of both germinal-vesicle breakdown (GVBD) and polar-body extrusion (PBE) as well as enlarged polar bodies. However, the shorter PFSA, perfluorobutanesulfonic acid (PFBS), and all PFCA did not show similar adverse cytotoxicity. Further, we found that 600 μM PFHxS and PFOS exposure induced excess reactive oxygen species (ROS) and decreased mitochondrial membrane potential (MMP). Cytoskeleton analysis revealed that PFHxS and PFOS exposure induced chromosome misalignment, abnormal F-actin organization, elongated spindle formation, and symmetric division in the treated oocytes. These meiotic defects compromised oocyte developmental competence after parthenogenetic activation. Conclusions:Our study provides new information on the structure-toxicity relationship of PFAS.

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Mitochondrial dysfunction in reproductive and developmental toxicity

Cited by 2 publications

References 168 publications

Adverse PFAS effects on mouse oocyte in vitro maturation are associated with carbon-chain length and inclusion of a sulfonate group

Adverse PFAS effects on mouse oocyte in vitro maturation are associated with carbon-chain length and inclusion of a sulfonate group

Adverse PFAS effects on mouse oocyte in vitro maturation are associated with carbon‐chain length and inclusion of a sulfonate group

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